A variety of plant hemagglutinins (lectins) have been shown to be an effective tool in detecting changes in membrane structure induced in a variety of cell lines. The transformation of cells by oncogenic viruses is associated with dramatic changes in the surface of the membrane. The new receptor sites exposed by (or associated with) infection and transformation by oncogenic viruses can be examined by their ability to agglutinate in the presence of lectins. Normal, non-neoplastic cell lines, are much more resistant to agglutination although they can be made susceptible by mild proteolytic treatment. The relationship of changes in membrane structure in neoplastic cell lines to other biochemical effects associated with cancer is a subject for intensive study in many laboratories. This work proposes to study the mechanism of action of a highly toxic lectin, ricin, isolated from castor beans (Ricinus communis). Ricin has been used to a considerable extent in exploring the difference between normal and neoplastic cells. Ricin is able to suppress the growth of Ehrlich ascites cells in mice and is some 50 to 100-fold more toxic to tumor cells than to normal cells. We are interested in two main areas: 1. how ricin is transported through the membrane and why it preferentially shows toxicity to transformed cells, and 2. how it acts once it penetrates the cell. At the present time, we known that ricin inhibits protein synthesis of eukaryotes by reaction with the 60S ribosomal subunit. We plan to investigate in further detail the reactions that it catalyzes within the cell at the polysome level. We want to know which ribosomal protein is the target of ricin and how cessation of ribosome action is achieved. A long term objective of this research is to determine whether ricin can be modified in some manner that would enable its use as a therapeutic agent in cancer treatment.